Cancer mortality-to-incidence ratio among Iraqi citizens: Nine-year National Estimates (2012-2020) and its relation to population growth rate and health expenditure

Background: Cancer continues to be a significant worldwide health concern with substantial mortality. The cancer mortality-to-incidence ratio (MIR), a proxy measure of observed five-year survival, can serve as a valuable indicator of cancer management outcomes and healthcare disparities among countries. This study aims to determine the MIR trend for all cancers combined among Iraqi citizens during 2012-2020 for health expenditure percentages out of the gross domestic product (e/GDP (%)) and population growth rate. Methods: The study used the Iraqi Cancer Registry annual reports for cancer data and World Bank data for health expenditure and population growth. Simple linear regression analysis examined the relationship between health expenditure, growth rate, and MIR, while joinpoint regression analysis examined the trend over time. The Ethics Committee of the College of Medicine at the University of Basrah approved the study. Results: An increasing trend in crude incidence rates for all cancer types combined was seen with a decrease in mortality rates from 2012 to 2020 in both sexes. A non-statistically significant reduction in MIR was found with an average annual percent change (AAPC) of -3.1% (P = 0.100). The decrease in MIR was higher among females than males, with a statistically significant difference (P = 0.003). High health expenditure presented as e/GDP (%) was associated with a favorable cancer survival rate, but this was not statistically significant (R2 = 0.263, P = 0.158). In contrast, a low growth rate was significantly associated with cancer patients’ survival (R2 = 0.505, P = 0.032). Conclusions: As indicated by the MIR and the MIR complement (1-MIR), the proxy five-year survival rate is improving in Iraq with time. Although not statistically significant, high health expenditure favorably affected overall cancer survival. A low growth rate, on the other hand, significantly improves cancer patients’ survival.

The mortality-to-incidence ratio (MIR) is an index that assesses the impact of cancer on the community and illustrates how well the healthcare system performs concerning patient care and cancer outcomes. 9The International Agency for Research on Cancer Registration (IARCR) manual proposed that if cancer registries could not estimate survival directly through comprehensive follow-up of all patients with cancer who had been registered to determine their vital status, the MIR could be used as an alternative indicator of survival. 10he lack of active monitoring through populationbased cancer registries, particularly in developing countries, hinders efforts to build reliable five-year cancer survival estimates.As a result, several studies examined the validity of MIR or MIR complement [1-MIR] as a valuable predictor of cancer survival.In their research, Sunkara and Hebert described the MIR as a helpful indicator for cancer screening and care in colorectal cancer patients. 11Similarly, Stenning-Persivale et al. reported that the 1-MIR is an appropriate tool for approximating observed five-year survival for the ten types of cancers studied. 12Ellis et al., on the other hand, stated that the inherent variability in the sensitivity of the MIR to changes in survival and the level of survival at any time since diagnosis between cancers of different lethality invalidates the 1-MIR as a survival measure. 13he likelihood of a patient surviving cancer is significantly increased by earlier detection and more effective treatments. 14However, more expensive healthcare is needed for screening tests and more potent treatments.Moreover, public health organizations may become overburdened and unable to offer adequate care as the population increases. 15][18] Iraq is categorized as an upper-middle-income country.Iraq's economy has suffered decades of political unrest and fluctuating oil prices, resulting in exceptional challenges and damage to the health system.However, over the last decade, Iraq has witnessed some improvements in its health outcomes despite the conflicts. 19According to World Bank Data, the per capita health expenditure

INTRODUCTION
Globally, there has been a rapid increase in both the incidence and mortality rates of cancer patients attributed to various risk factors, including population growth, aging, and socioeconomic development.Studies reveal that individuals residing in industrialized nations have a two to three times higher chance of developing cancer compared to those in underdeveloped countries.This is primarily due to differences in life expectancy, educational achievement, wealth, early detection and treatment of cancer, and improved registration. 1,2However, around 70% of cancerrelated deaths occur in low-and middle-income countries.Numerous studies and data from cancer registry reports indicated that Iraqi people are at an increased risk for developing cancer. 3,4e incidence rate (IR) of cancer in Iraq has increased from 38.91 per 100,000 people in 1994 to 78.93 per 100,000 people in 2020. 5The actual cause of this apparent increase is uncertain, at least for a few cancer types.However, the implementation of early detection programs for specific cancers or improved diagnosis and reporting, population aging, lifestyle changes, environmental damage caused by wars, and economic sanctions are probable factors. 3,6alth policymakers must develop programs utilizing epidemiological indices to calculate the disease burden in the community to control, prevent, and treat cancer. 7The incidence rate, death rate, and population-based cancer survival are three indices that make up a crucial instrument for estimating the burden of cancer.Moreover, variations in these indicators over time can reflect healthcare quality. 8ncreased from 173.19 USD in 2012 to 202.31 USD in 2020), 20 and the e/GDP grew from 2.69% in 2012 to 5.08% in 2020. 21 To the best of the authors' knowledge, no previous study in Iraq has used data from population-based cancer registries to estimate the national survival rate of all cancers combined.Therefore, this study was conducted to determine a nine-year time trend (2012-2020) of the MIR for all cancer patients combined in Iraq as an alternative survival measure and the impact of health expenditure presented as e/GDP (%) and population growth rate on it.

Study Design
This is a retrospective, registry-based study that includes data on cancer cases and deaths reported during the period 2012-2020.

Data Sources and Collection
The data used in this study was obtained through a review of the official Iraqi Cancer Registry (ICR) annual reports, which are publicly available at (https://moh.gov.iq/?page=35).The primary anatomical sites of all cancer types were identified and coded according to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3).The reported data included cancer incidence and mortality rates by sex and type of cancer recorded by the Iraqi Cancer Board, Ministry of Health and Environment, for 2012-2020.They are exclusive to Iraqi nationals and do not apply to expatriates working in Iraq.The data for Iraq's health expenditure out of GDP (e/GDP (%)) during the studied years was obtained from the World Bank Data. 21The data for the Iraqi population growth (annual %) during the studied years was obtained from the World Bank Data. 22

Definition of Indicators
Gross domestic product (GDP): It is "an economic indicator that measures the monetary value of the total goods and services produced within the borders of the country during a specific period (typically one year)". 23ealth expenditure as a percentage of the gross domestic product (e/GDP (%)) is the percentage of total general government expenditure on health. 24opulation growth rate refers to the ratio between the annual change in the population size and the total population for that year, usually multiplied by 100. 25
No statistically significant decrease was noticed in the MIR over time.It decreased from 0.49 in 2012 to 0.33 in 2020 with an AAPC of -3.1 (P = 0.400).
In contrast, the incidence rate increased with time (Figure 2).The MIR estimates were negatively but not significantly associated with e/GDP (R 2 = 0.263, P = 0.158).This means that the more resources are allocated to health, the more patients diagnosed with cancer will survive.The regression is Y = 0.48-0.04*x.For a 1-unit increase in e/GDP, there is a 0.04-unit decrement in MIR (Figure 3). Figure 4 demonstrates a statistically significant positive association between the annual population growth rate and a higher overall cancer MIR with an R 2 value of 0.505, P = 0.032 (meaning that the annual growth rate explained 50.5% of the total variability in the MIR).The regression formula is Y = 0.19+0.05*x.For every 1 unit increase in growth rate, there was a 0.05 unit increment in MIR.

DISCUSSION
Understanding population survival is critical both for individuals and public health.Given the scarcity of comprehensive population survival studies, estimating survival based on the complement of mortality and incidence ratios is an option. 9his study revealed that during the study period (2012-2020), the overall trend of MIR has not significantly decreased, with an AAPC of -3.1% p = 0.400, indicating an increase in survival for all cancer patients combined.The median of the MIR of all cancers combined in Iraq for that period was 0.33 for both males and females (0.38 for males and 0.28 for females), giving an overall MIR complement (1-MIR) or a proxy 5-year survival rate of 0.67 or 67% [0.62 (62%) for males and 0.72 (72%) for females].It is better than that reported for Brazil from 2002 to 2014, which was 52% for males and 56% for females. 27This difference could be partly explained by the fact that our study looked at a different time frame

Statistical Analysis
All incidence and death rates were crude rates and expressed per 100,000 persons.The cancer incidence rate for each calendar year of the study refers to the patients diagnosed with cancer in that year, depending on pathology reports.The cancer mortality rates were presented for people certified as having died from cancer in that year.
The MIR for all cancer types combined was calculated by dividing the crude mortality rate by the crude incidence rate for all cancer types for each year of the study period and comparing them to the annual population growth rate and e/GDP (%).The 1-MIR was evaluated as a proxy measure for the 5-year relative survival in the same calendar period for all cancer types combined registries. 11he median was used to measure the central tendency to obtain an overall assessment of the distribution of the MIR.It was calculated as total and for males and females separately.The AAPC in MIR was computed to evaluate the magnitude and direction of the trends using the National Cancer Institute's Joinpoint Regression software program (version 4.9.1.0). 26 simple linear regression analysis was done using the IBM Statistical Package for the Social Sciences (SPSS) for Windows, Version 24.0.(IBM Corp., Armonk, N.Y., USA), taking the MIR as the dependent variable and annual population growth rate and e/GDP (%) as the independent variables.P values <0.05 were considered statistically significant.Scatter plots were made using Microsoft Excel 2019.

RESULTS
The overall incidence rate of cancers during the 9-year study period was 74.

Figure 4. The association of mortality-to-incidence ratio (MIR) with population growth rate %)
than the Brazilian study, or it might result from an improvement in the quality of treatment.Our results are comparable to that in Australia.Based on data sourced from the Australian Institute of Health and Welfare Cancer (2020), the overall MIR for all cancers combined for the period 2012-2019 was 0.34 for both males and females, 0.35 for males, and 0.33 for females, giving a survival rate of 66%, 65%, and 67%, respectively. 28he level of completeness of Iraqi death certificates may preclude a meaningful comparison.Nevertheless, the reliability of death registration would be questioned when a condition such as a constant mortality rate was reported. 29Additionally, VOL.2023 / ART.38   Cancer mortality-to-incidence ratio among Iraqi citizens: Nine-year National Estimates (2012-2020) increase in cancer mortality appears to be slowing. 36Hashim et al. reported that the mortality rate for most cancers stabilized or decreased after the age of 85, particularly for non-hormonal cancers.Whether this represents an organic leveling of mortality rates or a reduction in the validity of most cancers' registration at the various oldest old is debatable. 37imilarly, Caroli et al. observed that between 1970 and 2015, the age-standardized mortality rates for all cancers combined showed a heterogeneous but widespread decline in their study of the mortality time trends of 17 cancer types in 11 38 It seems that general senility, restricts cell proliferative potential and the angiogenesis necessary for tumor growth, affects the severity of cancer in old age. 36The factors that could the patterns of cancer mortality among elderly patients include the presence of comorbidities, less intensive screening, reduced aggressive treatment, disease misclassification, and alterations in the underlying risk factors like hormones. 37here are a few limitations to consider with this study.Firstly, there may be some incompleteness in death registries, which cannot be completely ruled out.Secondly, some inaccuracies about the cause of death may occur, particularly among the elderly.Most cancer patients do not die as a result of their disease, and for those who do die, the duration of survival varies widely. 39espite these limitations, this is the first study that establishes the MIR of cancers and its 9-year trend in Iraq, and it offers a distinctive viewpoint on the relationship between MIR of cancers and e/GDP and annual population growth rate.MIR is a simple and quick indicator that can provide important information relevant to the local impact of cancer and be applied as a relative marker of cancer care and the performance of a country's overall health system, 11 even though its exact role is still debatable because it would never replace the importance of survival data from cohort surveys. 13

CONCLUSION
Following the findings of previous studies in some countries, 40,41 the results of this study showed that the incidence of cancer in Iraq the survivorship of diagnosed cancer cases that have been officially registered in the ICR is estimated through cancer patient follow-up and routine reviewing of the relevant death records. 30ven so, it is still possible that the actual number of cancer deaths was underestimated.
Our study found that the survival was statistically higher for female than male cancer patients (the medians were respectively 72% versus 62%, p = 0.003).This result is in agreement with what was reported by Zhua Y et al., who indicated that male cancer patients have higher mortality rates and shorter survival times than female patients. 31The observed differences have complex causes, but they can be attributed to behavioral factors such as smoking and alcohol consumption, delayed diagnosis, sex chromosomes, and sex-biased molecular changes. 32A negative but not statistically significant linear relationship was found between the e/GDP and the MIR (R 2 = 0.263, P = 0.158).A similar result was reported by Lee et al., who found no statistically significant association between pancreatic cancer MIR and e/GDP. 33However, Ades et al. observed that the more budget spent on health, the fewer the deaths of cancers, and a statistically significant correlation was found between MIRs of all cancers and % e/GDP (r = -0.4726,P = 0.013). 24imilarly, Batouli et al. found that cancer MIR in high-income countries (0.47) was significantly lower than that of middle/low-income countries (0.64), with a p<0.001. 34In high-income countries, the total health expenditure showed a statistically significant inverse relationship with the overall cancer MIR (P <0.001).Better or more frequent screening programs in countries with higher e/GDP lead to increased cancer diagnosis, early detection, and treatment, thus raising the reported incidence and lowering mortality. 33he annual population growth rate and MIR were found to have a statistically significant positive relationship (R 2 = 0.505, P = 0.032).The relationship between population growth and MIR is complex and multifactorial.Longer life expectancy and lower birth rates, on the other hand, are associated with an aging population, which has an impact on the extent of cancer incidence. 35

SOURCE OF FUNDING
None.

CONFLICT OF INTEREST
None of the authors declares a conflict of interest.
during 2012-2020 increased while there was a decrease in mortality rates.As indicated by the MIR and the MIR complement (1-MIR), the proxy five-year survival rate is improving in Iraq with time.Females showed significantly better cancer outcomes than males.High health expenditure as a percentage of GDP favorably affected overall cancer survival, though this relationship was not statistically significant.While a low growth rate significantly increases cancer patient survival.The findings of this study could help policymakers evaluate current laws and

Table 1 . Certain Iraqi economy and health expenditure indicators during 2012-2020
GDP = Gross Domestic Product, e/GDP = Health expenditure out of Gross Domestic Product (quoted from the World Bank Data).

Table 2 . Overall IR, MR, MIR, 1-MIR for all cancers combined in Iraq during 2012-2020 and by sex
IR = incidence rate, MR = mortality rate, MIR = mortality incidence ratio.
While mortality from noncommunicable diseases increases with age, such as cardiovascular disease, the age-related Cancer mortality-to-incidence ratio among Iraqi citizens: Nine-year National Estimates (2012-2020) develop effective cancer intervention strategies.Future cohort survival analysis research is required to assess the reliability of MIR in predicting the five-year survival of cancer patients in Iraq.